Stakeholder Meeting, 7 th June 2013 Considerations on the assessment - - PowerPoint PPT Presentation

Stakeholder Meeting, 7th June 2013 Considerations on the assessment of safety data originating from patient support programmes

Qun-Ying Yue; MPA, Sweden; PRAC member

Disclaimer

• The views presented in this presentation are

those of the author and should not be understood or quoted as being made on behalf of the EMA and/or its scientific committees.

• Views are presented solely to aid the discussion

and should not be interpreted as adopted guidance.

Background

• The mandate of the PRAC shall cover all aspects of the risk management of the use
• f medicinal products for human use including

– the detection, assessment, minimisation and communication relating to the risk of adverse reactions, – having due regard to the therapeutic effect of the MP for human use, – the design and evaluation of PASS and pharmacovigilance audit.

• PRAC tasks common to both centrally and non-centrally authorised products:
• (i)

For Union procedures triggered for safety reasons: PRAC recommendation.

• (ii)

For PSUR single assessment: PRAC shall issue a recommendation.

• (iii)

For imposed PASS protocols: the PRAC shall issue a letter of endorsement or

• bjection.
• (iv)

For imposed PASS study results: the PRAC shall issue a recommendation.

• (v)

For signals: the PRAC shall issue a recommendation.

• (vi)

For EURD and frequency of PSURs submission: PRAC shall be consulted.

• (vii)

For list of MP requiring additional monitoring: PRAC shall be consulted.

• (viii)

For “for cause” pharmacovigilance inspections: PRAC shall issue an advice.

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Pharmacovigilance data

• High quality data collection is a prerequisite for

signal detection and assessment.

• PSPs are not a single well defined entity but a range
• f activities
• The fundamental legal obligations apply regardless
• f the juxtaposition of activities involved in any

given PSP

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Individual Case Safety Reports from PSPs

• If Individual Case Safety Reports (ICSRs) come from

PSPs on an ongoing basis as 15 day reports - what are the issues?

• If ICSRs come from PSPs as boluses of data

(because they were derived from studies or post hoc data analsys, or as corrective action following non- compliance)?

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(Hypothetical) Scenario

• Medical impact analysis for unreported adverse

reactions cases from Patient Support Programmes

• Structured analysis /assessment
• 1. Fatal cases
• 2. Risks in the RMP or reactions subject to ongoing

monitoring/review in PSURs

• 3. Other important adverse reactions

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(Hypothetical) Scenario

Assessment on B/R impact analysis Uncertainties - cases poorly documented, limited value for signal/risk assessment

• Number of PSPs and number of patients included
• Follow up if sufficient details available (for patient or reporter)
• Cases contain limited information (medical history, time to
• nset, indication and cause of death).
• Reports from non health care professionals
• Limited information precludes meaningful causality

assessment

• Potential impact on BR profile cannot be completely assessed.

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(Hypothetical) Scenario

Conclusions and recommendations

• n B/R impact analysis

Scenario 1 - No further action is required – No issues identified that have impact on ongoing monitoring activities – not warrant an update to PI or RMP. – Overall B/R unchanged and positive. – Monitor certain issues in subsequent PSURs / Continued routine pharmacovigilance.

• Reactions are covered in PI.
• Low number of cases (vs total number in database);
• Isolated reactions; non-serious cases
• No new or changing safety signals can be identified

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(Hypothetical) Scenario

Conclusions and recommendations

• n B/R impact analysis

Scenario 2 - Further requests needed:

• procedures for ensuring adequate processing and

follow-up of cases from PSPs to ensure case quality, to allow a reasonable causality assessment.

• approach to identify relevant reactions from the

database

• measures taken to better document cases.

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Reflections

• Role for PSP reports in signal detection

Further questions (1):

• What influence do the reports originating from the

PSPs have on the overall safety data for signal detection? – Some products have PSPs and others do not. How do reports originating from PSPs impact on the ability to identify potential safety issues in signal detection? – How to integrate PSPs in the routine monitoring

• f safety of medicinal products?

– How to improve the quality of data to help signal detection and safety issue assessment?

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Reflections

• Role for PSP reports in signal detection

Further questions (2):

• Relative value of ICSRs quality versus ICSRs

quantity – What about the quality of the reports? – What are the challenges for causality assessments for the PSPs reports? – Causality assessment is essential for signal detection. – Improved quality of reports from PSPs is essential for assessors.

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Reflections

• Role for PSP reports in signal detection

Further questions (3):

• The impact of data not being collected or included

into global PV systems is an ‘unknown unknown’ and this makes things difficult for assessors and inspectors.

• The impact of the data available may be different.
• QPPV/pharmacovigilance should have oversight of

what arrangements marketing departments and service providers are putting in place for these programmes (and collection of safety data from the programmes).

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Reflections

• Role for PSP reports in signal detection

Further questions (4):

• How to best arrange the signal detection with the

knowledge that there are PSP ongoing for a product?

• Can a signal detected from spontaneous reports be

ascertained with cases originating from PSPs?

• Can a signal with rare events be identified from reports
• riginating from PSPs?
• Do we need to wait for new spontaneous reports to

react?

• Minimum quality of reports is required for safety

surveillance of medicinal products, which allow for early identification of safety issues.

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Reflections - Role for PSPs in Risk Management Plans

• Generation of safety data is largely a by-product of

PSPs rather than the objective.

• If there is a need to demonstrate safety or

investigate/ characterise a risk, presumably the preferred option is a well designed study with a clear research question, analysis plan etc.

• PSPs should not be used as the principal way to

collect safety information in the frame of RMPs.

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In summary - Role for reports of suspected adverse reactions originating from PSPs

• The impact of the data available from PSP may be

different.

• Causality assessment is essential to report true

cases of suspected adverse reactions to competent authorities

• Improved quality of reports from PSP is expected.
• PSPs should not be the principal mechanism to

collect safety information in the frame of RMPs.

• Safety concerns should be addressed in the context
• f well-defined studies with protocols.

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